DAYBREAK: Phase 2 Study in Patients With Specific Gene Defects in the MC4R Pathway

Overview

About this study

To evaluate the proportion of obese patients with genetic defects in the melanocortin-4 receptor (MC4R) pathway who achieve a clinically meaningful reduction in body weight in response to setmelanotide after an initial response to open-label treatment

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

 Inclustion Criteria:

  • Patients must have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity.

For a gene variant to be eligible for inclusion in the study, the variant must be categorized by a CLIA/CAP/ISO15189 -certified laboratory using ACMG criteria as (1) Pathogenic, (2) Likely Pathogenic or (3) a VUS. In the case where an investigator has genetic results on a patient who may be eligible for the study, but the genetics have not yet been categorized by a CLIA/CAP/ISO15189 -certified laboratory, then the Sponsor may provide testing and/or categorization through a third-party laboratory.

  • Patients between the ages of 6 and 65 at the time of signing Informed Consent or Assent are eligible for the study.
  • Patients must be obese, defined as BMI ≥40 kg/m2 for patients ≥18 years of age or BMI ≥97th percentile for age and gender for patients 6 up to 17 years of age based on based on the US Centers for Disease Control and Prevention criteria.
  • Study participant and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the study (including QD injection regimen and all other study procedures) and is able to understand and sign the written informed consent/assent. Patients who are unable to comply with all study procedures due to cognitive limitations or any other reason should not be enrolled into the study.
  • If male or a childbearing female, including pre-pubertal females if relevant, the patient must agree to use a highly reliable form of contraception throughout the study and for 90 days following the study.
  • Highly reliable acceptable forms of contraception include hormonal (i.e., oral, implantable, or injectable) AND single-barrier method (i.e., condom), or an intrauterine device (IUD) AND single-barrier method (i.e., condom) or vasectomy/vasectomized partner. True abstinence is acceptable only if it is the preferred and usual lifestyle of the patient. Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening follicle-stimulating hormone [FSH] level in the post-menopausal lab range), and failure to have achieved menarche, do not require contraception during the study. Female patients must not become pregnant and male patients must not donate sperm during and for 90 days following their participation in the study.

Exclusion Criteria:

  • Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in > 3% weight loss.
  • Use of any medication that is approved to treat obesity within 3 months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion).
  • Note: Glucagon-like peptide-1 (GLP-1) receptor agonists may be used up to the dose approved for the treatment of diabetes mellitus (e.g., liraglutide up to a daily dose of 1.8 mg) as long as (1) it is not being prescribed for the treatment of obesity, (2) the dose has been stable for at least 3 months prior to enrollment, (3) the patient has not experienced weight loss during the previous 3 months, AND (4) the patient intends to keep the dose stable throughout the course of the study.
  • Bariatric surgery within the previous 6 months. Note: Patients with a history of gastric bypass surgery should have documented evidence of stable weight, defined as weight loss in the last 3 months of < 3% of body weight.
  • Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance.
  • Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) during Screening, any suicide attempt in the past 20 years or any suicidal behavior in the last month.
  • Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results. Any patient with a potentially clinically significant disease should be reviewed with the Sponsor to determine eligibility.
  • Has significant features of (or meets the diagnostic criteria for) a genetic syndrome that is associated with obesity, such as Tatton-Brown-Rahman syndrome (DNMT3A), Rett Syndrome (MECP2), Chung-Jansen syndrome (PHIP), Schaaf-Yang syndrome (MAGEL2), ulnar mammary syndrome (TBX3), or Rubinstein-Taybi syndrome (CREBBP).
    • Note: Although some of the genetic variants that are eligible to be enrolled into this study are associated with specific syndromes, the intent of this study is not to enroll children with significant cognitive impairment or other significant co-morbidities. Patients with the correct genetic variants, but who otherwise do not exhibit the syndrome, are eligible for enrollment.
  • HbA1C > 10.0% at Screening.
  • History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
  • Glomerular filtration rate (GFR) < 60 mL/min at Screening.
  • History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism.
    • Note: If the type of skin cancer is not known, then the patient should not be enrolled into the study.
  • Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of a comprehensive skin evaluation performed by the Investigator during Screening. Any concerning lesions identified during Screening will be biopsied and results known to be benign prior to enrollment. If the pretreatment biopsy results are of concern, the patient may need to be excluded from the study.
  • Patient is, in the opinion of the Study Investigator, not suitable to participate in the study.
  • Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
  • Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
  • Significant hypersensitivity to any excipient in the study drug.
  • Females who are breastfeeding or nursing.

Eligibility last updated 4/8/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Andres Acosta, M.D., Ph.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Jessica Stutzman

(507) 422-5891

RSTINDIVOBESITY@mayo.edu

More information

Publications

Publications are currently not available
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